International Journal of Nursing

Effect of massage the rapy on postoperative and in patients receiving

Journal: International Journal of Nursing Practice

ManuscriptFor ID: PeerDraft Review

Manuscript Type: Research Paper

Key Words: cancer, nausea, vomiting, massage, Systematic Review

Page 1 of 12 International Journal of Nursing

1 2 3 Effect of massage therapy on postoperative nausea and vomiting in cancer patients receiving 4 5 chemotherapy: a systematic review 6 Farnoosh Rashvand 1, Nahid Dehghan Nayeri 2, Nazila Javadi Pashaki3 7 8 Abstract 9 10 Introduction: Nausea and vomiting are the most common and most annoying physical side 11 effects of chemotherapy and massage therapy is one method to reduce these effects. However, 12 13 because these studies were conducted with different designs and have shown different effects on 14 different populations, the objective of this study was to systematically study which has examined 15 the effect of massage therapy on nausea and vomiting in cancer patients receiving chemotherapy 16 until 2014. 17 18 Methods: In order to determineFor the Peer effect of massag Reviewe therapy techniques on nausea and vomiting 19 in cancer patients undergoing chemotherapy, all articles on these subjects to 2014, such as 20 Electronic Information CINAHL, British Nursing Index, EMBASE, AMED, PsycINFO, 21 22 PubMed, SIGLE, Google scholar, CancerLit and site of Chochrane were searched, and finally 23 according to inclusion criteria, 14 articles remained using relevant keywords based on clinical 24 and quasiexperimental trials on nausea and vomiting. The results of all relevant studies were 25 tested by two researchers and based on the checklists of evaluation studies of clinical and quasi 26 experimental trials and criteria for entry into the study, 6 studies were removed and 8 of them 27 were remained. 28 29 Conclusion: Only two of the 8 studies did not show significant results regarding the effect of 30 31 massage therapy on nausea and vomiting in cancer patients undergoing chemotherapy. 5 studies 32 of 8 studies on women with , a study of gynecological and two studies were 33 conducted on other types of cancers. Given that no studies have been conducted on various types 34 of cancer and chemotherapy, therefore, more randomized controlled trials are seems to evaluate 35 and determine the effectiveness of massage therapy. 36 37 Keywords : "cancer," "nausea," "vomiting" and "massage" Systematic Review 38 39 Introduction 40 41 Cancer is the most frightening of all diseases including cardiovascular disease. Often, the term 42 are considered synonymous with death, cancer, pain, deformity, and dependency. Cancer is a 43 global problem that affect people without regard to race, sex, age, socioeconomic status or 44 cultural causes and causes 552,200 deaths annually (LEWIS, 2000). 45 46 In Iran many of cancer patients have undergoing chemotherapy annually. Cancer in general is the 47 third largest cause of death. Annually, more than 30,000 people lose their lives due to cancer. It 48 49 is estimated that each year more than 70,000 new cases of cancer occur in countries, and with 50 increasing life expectancy and the aging of the population is expected cancer cases on the next 51 two decades be double. (Institute for Research, Education and 2012). 52 53 1 54 Nursing Education PhD student, School of Nursing and Midwifery, Tehran University of Medical Sciences 2 55 Professor of Nursing and Midwifery Care Research Center, School of Nursing and Midwifery, Tehran University 56 of Medical Sciences, * Corresponding Author: [email protected] 3 57 Nursing Education PhD student, School of Nursing and Midwifery, Tehran University of Medical Sciences 58 59 60 International Journal of Nursing Page 2 of 12

1 2 3 One of the main treatments for cancer is chemotherapy. A successful course of chemotherapy 4 5 may be associated with side effects such as nausea, vomiting, , fluid and electrolyte 6 imbalance, , decreased gastrointestinal mucosa of patients intolerant to treatment, 7 and even refusing to be treated (Yoo HJ, Ann SH, Kim SB, 2005). 8 9 Nausea and vomiting are the most common and most annoying physical side effects of 10 chemotherapy (Carner j, Baily C, 2001). Uncontrollable nausea and vomiting can cause delays in 11 the periodic program in chemotherapy and clearly reduce the quality the patient's life (Deborah 12 Hughes and et al 2008). In a study, the incidence of nausea and vomiting after chemotherapy 13 14 44.2 percent was expressed. On the other hand, 1 25 % of patients receiving chemotherapy 15 induced nausea and vomiting caused by cancer treatment, refuse treatment (Grundy M.2001). 16 17 Despite advances in medical therapy, cancer patients undergoing chemotherapy as experience 18 treatmentrelated side For effects, including Peer nausea, Review fatigue, , and pain. Although the anti 19 nausea medications are prescribed to prevent nausea and vomiting in patients who often are 20 selective antagonists, but most patients are resistant to these treatments. It is estimated 21 that more than 60% of patients who receive chemotherapy despite drugs, suffer from 22 23 the condition (Griffiths & Klein 2004). Several randomized controlled trials studies on the effect 24 of complementary therapies on the effects of chemotherapy ever done, preliminary evidence 25 suggests that complementary therapies may be reduce symptoms of chemotherapy and improve 26 the health of patients. (Janice PostWhite and et al, 2003). However, because these studies were 27 conducted with different designs and have shown different effects on different populations need 28 to examine the effect of these studies. 29 30 New research suggests that patient to comply with medical conditions frequently seek medical 31 32 interventions that are capability to perform outside of the clinic and is called complementary and 33 alternative therapies. (Ahles TA, Tope DM, Pinkson B.1999). Massage therapy is one of 34 complementary medicine which has highest rates of use in complementary therapies in cancer 35 patients. Massage therapy reduces stress like cortisol, epinephrine and norepinephrine 36 and thus reduce anxiety and nausea and vomiting and creates relaxation and has been used as the 37 most common way of complementary and alternative medicine for health promotion and 38 39 prevention of diseases in acute and chronic conditions (Deborah Hughes and et al 2008). 40 There is a set of empirical evidence and case study reports (Johnston, 1996; Refuge in 1995, 41 42 West 1994, Wright 1999, Manzoli 2001) that support the use of massage therapy in cancer care 43 and introduce its benefits for cancer patients, reduced the level of relieve anxiety and emotional 44 stress, pain, muscle tension and fatigue (Campbell 2001). 45 46 Although several studies have been done in this area, yet has not given a definitive answer to the 47 question of what effect massage on nausea and vomiting. In addition to the above, study the texts 48 show there is no credible evidence of tumor spread through massage therapy, but health care 49 providers should know although massage therapy is safe, but may have many disadvantages for 50 51 some patients (Corbin 2005). Thus, a systematic review in this regard could be helpful. The 52 objectives of this systematic review include: 1. the effect of massage therapy on postoperative 53 nausea and vomiting in cancer patients undergoing chemotherapy treatment according to the type 54 of massage therapy (Swedish massage, aromatherapy, reflexology, acupressure, and touch), 2. 55 The effect of massage therapy on nausea and vomiting in cancer patients undergoing 56 57 chemotherapy according to the type of gastrointestinal or nongastrointestinal cancer 3. The 58 effect of massage therapy on nausea and vomiting in cancer patients receiving chemotherapy, 59 60 Page 3 of 12 International Journal of Nursing

1 2 3 depending on the type of chemotherapy regimen, and is an answer to this question: does the 4 5 nausea and vomiting massage reduces chemotherapy in cancer patients? 6 7 Methods and Findings 8 The present study is a systematic review in which all studies that were in regard to the effects of 9 10 massage therapy on postoperative nausea and vomiting in patients undergoing cancer treatments 11 until 2014 had been done, were searched by the key word "cancer," "nausea," "vomiting" and 12 "massage treatment "strategy Chochrane the databases CINAHL, British Nursing Index, 13 EMBASE,, PubMed, AMED, PsycINFO, SIGLE, Google scholar CancerLit Chochrane 14 sites. Search basis was based on select clinical trials and quasiexperimental studies that their 15 abstracts were published in English and Persian. Inclusion criteria were as follows: a quasi 16 17 experimental studies, before and after randomized controlled clinical trials with the issue of 18 massage therapy in cancerFor patients Peer undergoing Review chemotherapy and aged 18 to 65 years and 19 measured nausea and vomiting by a reliable and valid measurements, patients were not using any 20 complementary therapy other than standard treatment. `, the studies which had following criteria 21 were not evaluated: 1. those review these techniques as retrospective, 2. trials without control 22 23 Assessment of nausea and vomiting, according to the scales used in the authoritative references 24 was used, so that the repetition rate of nausea and vomiting were measured. In the literature 25 26 general, finally 14 studies were collected. Among the articles by topic, by two experienced 27 researcher examined and by the evaluation checklist (RCTs) of controlled clinical trials 28 CONSORT and with considering criteria for inclusion in the study, 8 articles were 29 selected. Characteristics of studies included in Table 1. The ultimate goal of all this research in 30 methods and dependent variables (nausea and vomiting) have a common points. Among the eight 31 32 studies, a study on the effect of Swedish massage, a study of the impact of soft strokes, a study of 33 the impact of effleurage strokes and 5 studies on the effect of acupressure which were a form of 34 massage had examined nausea and vomiting in patients undergoing chemotherapy: 35 36 1. randomized controlled trial Billhult (2007) with the aim of detecting the effect of massage 37 pressure in women with breast cancer were performed in the six areas of nausea, anxiety, 38 depression, quality of life, stress and cellular immunity. Inclusion criteria included a diagnosis of 39 breast cancer, female gender, being on the list of chemotherapy. In all patients, an antinausea 40 drugs and a were given. Massage was performed from the behind to the trailing 41 42 limb. Patients were randomly assigned to a massage therapy group (20 minutes in 5 innings of 43 massage) or control group (a five 20 minute visit). Massage were followed by 5 nurses and 44 practical nurses after theoretical and practical training. Massage was conducted as a soft blows 45 for 20 minutes and by cooled vegetable oil. The control group were visited only by one of the 46 hospital staff for 20 minutes. All conditions were the same except for the intervention. Measured 47 48 outcomes included nausea and VAS on a scale of 100 mm, before and after intervention were 49 measured every 5 sessions. Data were analyzed using ttests (to determine differences between 50 groups) and Bartlett's test (to determine inequality of variances for the groups) and software EpI 51 Info. The results showed that the massage reduced vomiting of the intervention group compared 52 with the control group (MannWhitney test, the average percent of recovery = 3.32 ± 73.2 53 percent). The study shows that massage can be beneficial in patients undergoing chemotherapy, 54 55 but the need to confirm the results by studies with larger volumes are listed in this study. 56 57 2. Study of PostWhite (2003) was conducted as randomized controlled cross over 58 trial. Inclusion criteria included adult patients from two outpatient chemotherapy clinics with a 59 60 International Journal of Nursing Page 4 of 12

1 2 3 diagnosis of cancer who have remained two or more cycles of chemotherapy and also has score 4 5 3 of 10 or higher than in the report of nausea. Patients were randomly assigned to one of three 6 groups: massage therapy, therapeutic touch group (energy healing) and received care. All those 7 were received four 45minute sessions of the set interventions per week and four times a week a 8 standard / control care. The first session of the intervention or control began before the first cycle 9 of chemotherapy in the treatment. After four weekly sessions, participants were replaced in the 10 11 intervention groups. The mean time between weekly visits was from 6.9 to 7.2 days and the 12 average time between cross periods 16.7 days (range, 3 to 56 days). Assessing the nausea and 13 self scoring the current vomiting was on a scale of zero to ten, just before and after each 14 intervention session. After 4 weeks, evaluation of intervention effects at the beginning and end of 15 session of each 4 week period, sessions 1, 4, 5, 8, was carried out. A Swedish massage protocol 16 with the same blows using massage gel Biotone, containing oils of apricot, grape and sesame 17 18 were performed. ParticipantsFor began Peer the massage Reviewin a prone position by effleurage strokes (gentle 19 rhythmic crawling strokes) to top of back and then by petrissage (relaxation massage) and rub 20 the waist, hips, buttocks continued distal organs. Massage and touch was avoided in the tumor 21 and surgery location. Nausea was measured as selfreporting using BPI instrument. 33 patients 22 due to request a different treatment or change in schedule, 30 patients due to changes in 23 24 treatment protocols and 3 patients because of death were also excluded. After loss of the samples 25 among 66 patients remaining 15, 21 and 30 patients were in the groups of massage, touch and 26 control, respectively. Nausea group had more loss than the study group in baseline. (Index score, 27 z = 2.04, P = 0.041) analysis revealed that the conditions received had no effect on outcomes of 28 interventions. Despite the meantime washout 7 to 16 days between the intervention conditions, 29 two outcomes with the transitional effect showed that response to variable of use of 30 31 (z = 2.15, P = 0.031) in the first period will affect the response to the second period. Therefore, 32 only data from the first period (sessions 1 to 4) were used to test the variables that leads to less 33 power to detect differences for the use of Ondansetron. The effects of the intervention on the 34 outcome of nausea factor during 4 weeks were compared with control group and no significant 35 differences between each intervention and control conditions in the index of nausea, nausea 36 37 interference or use of was observed. The samples despite nonsignificant expressed 38 nausea reduction after massage (table). 39 40 3 Study of Roscoe (2003) was done with the aim of determining the effects of pressure massage 41 and wrist bands Acustimulation for the relief of nausea and vomiting associated with 42 chemotherapy. Inclusion criteria included patients candidate for chemotherapy for the initial 43 treatment with the regimen included in the table. Randomization was done based on the 44 chemotherapeutic factor and clinical program location of the population. The patients 45 46 randomly was assigned in the groups of doublesided pressure bands (SeaBand) and separate 47 acustimulation band (Reliefband) or the control condition of without bond. All patients received 48 antiemetics on the day of treatment. inside of the wrist, about 2 inches elementary to Fold of skin 49 at the distal wrist between longus Palmaris tendons and carpi radialis flexor muscles was 50 wraped. The patients were instructed to wear the bands continuously for 5 days except when the 51 water is likely to penetrate. Nausea and vomiting were measured by daily reports of the 52 53 paitents. Each day was devided to 4 episodes (morning, afternoon, evening and night) and 54 patients reported severity of nausea and the number of vomiting occurnece for each period at 55 each day of treatment and 4 days later (generally 20 report time). Severity of nausea on a 7point 56 scale was evaluated with grades range from grade 1 for lack of nausea to grade 7 for severe 57 nausea. The following score showed four moderate nausea. Using ttest and chisquare, 6 58 59 60 Page 5 of 12 International Journal of Nursing

1 2 3 outcomes related to wrist bands performance were evaluated: Frequency of vomiting, nausea 4 5 peak intensity on the day of treatment (acute nausea), vomiting peak intensity during the second 6 to fourth days of treatment (delayed nausea) and the antinausea medications taken at 7 home. Initial analysis revealed that patients with compression bandages had significantly less 8 nausea on the day of treatment (mean 2.6) compared with control group (mean 3). Patients with 9 acustimulation band reported less nausea (p = 0.005). Antinausea pills taking was lower at a 10 11 pressure bandage group (5.1) compared with patients of the group without bond (9.7). But 12 statistically was not observed the difference in nausea and vomiting. This study support the 13 bands as a complementary therapy along with antinausea medication to control nausea caused 14 by chemotherapy. Patients of the pressure group had a lower nausea than the control group. This 15 reduction was not seen in delayed nausea. 16 4Pearl et al (1998) assessed performance of Acustimulation with a followup in a controlled and 17 18 randomized doubleblindFor placebo Peer crossover trial Review study. All patients participating in the study 19 received a standard protocol to treat nausea and were bandaged for 7 days continuously. Patients 20 in active bands cycles compared to placebo band cycle patients reported a significant reduction 21 in nausea during the second to fourth days after the treatment. The incidence and severity of 22 nausea and vomiting was similar for both groups. 18 patients were among the crossover of the 23 24 study. The mean age of crossover patients and their antiemetic dose was comparable with the 25 general population of the study (56.3 years against 58.6 and 22.7 versus 22.7 milligrams per 26 square meter per week). Although nausea was significantly less in active cycles during second to 27 fourth days, patients on average experienced less than one daily episodes of vomiting per 28 cycle. The researchers concluded that pressure bands are an effective complement for standard 29 antiemetic factors to control nausea caused by chemotherapy with in patients with 30 31 gynecological cancer. 32 5. Study Grealish, Laurie (1999) is a quasiexperimental study of use of foot massage on patients 33 34 with cancer. In a sample of 87 persons, foot massage was done and was measured with a visual 35 analog scale. The purpose of this study was to investigate the therapeutic effects of foot massage 36 as a complementary therapy. Objectives to measure the effect of foot massage was a subjective 37 experience of pain, nausea, and calm. To separate acute pain from , inclusion criteria: 38 a) cancer diagnosis b) age 18 years or more, c) pain and / or nausea, and d) the lack of any recent 39 40 surgery within 6 weeks and participation in the study with informed consent in accordance with 41 the standards of the local health department and the university ethics committee voluntarily. In 42 fact, 103 people were enrolled in the study, but 7 patients withdrew due to disease severity. In 43 addition, nine persons’ data were incomplete, so that the sample declined to 87 subjects, 52 44 females and 35 males (aged 18 to 88 years, mean 58.2 years). Participants under study were 45 46 massaged twice and in the third time were as the control of their group. Participants were 47 randomly assigned to one of three groups of agent control. Heart rate and subjective data, such 48 as pain and nausea were collected at two intervals: before the massage and 10 to 20 minutes after 49 the massage. Massage would take for 10 minutes (5 minutes for each leg). Massage was 50 performed from toes to the leg. In this study, it is often tried to control situations, however, no 51 control of the whole terms is the limitations of the study. Selfreporting of nausea was measured 52 53 using the VAS 100 mm. Average scores for heart rate (beats per minute), pain, nausea and 54 relaxation before and after were compared using the t test for related samples. Analysis of 55 variance (ANOVA) in three different modes, C (controlled before and after), M1 (first innings of 56 massage before and after), and M2 (second innings of massage before and after) were conducted 57 for each participant, with respect to gender as a factor for the research and the ttest was set with 58 59 60 International Journal of Nursing Page 6 of 12

1 2 3 86 degrees of freedom and statistical differences with a significance level of 0.05. Significant 4 5 difference was found between the pretest control session and nausea mean score declined from 6 18.4+ 22.5 mm to post test score 17.4 + 20.5 mm (T = 0.942, P = 0.1745). In contrast, nausea 7 mean score for massage session declined from 17.5 + 24.4 mm to 11.1 + 19.1 mm (t = 3.117, P = 8 0.0012), the mean difference is 6.4 mm. The result of data for session 2 was repeated with a 9 before massage nausea score of 17.7 + 23.6 mm and after massage nausea score 12.8 + 18.6 mm 10 11 (t = 3.178, P = 0.0011), with a mean difference of 4.9 mm. 12 6 The purpose of the study of Suh EE (2012) is to investigate the effect of P6 acupressure on 13 14 nausea and vomiting induced by chemotherapy in patients with breast cancer. This study is a 15 randomized clinical trial in cancer center at the University of Seoul, including 120 women 16 undergoing chemotherapy after breast cancer. Participants were randomly divided into four 17 groups: control group (who received placebo), the group that received only counseling, the group 18 that only received P6For acupressure Peer and the group Review that received P6 acupressure with nurse 19 consultations. Gastrointestinal discomfort experiences was measured by Rhodes index of nausea, 20 21 vomiting and retching including acute (1day) and delayed (days 2 to 5 days) observation of 22 CINV chemotherapyinduced nausea and vomiting. Significant differences was seen in 23 demographic and diseaserelated variables among the four groups. CINV levels were 24 significantly different in the two groups from day 2 to day 5. CINV difference mainly was 25 related to the difference between the two groups of control and P6 acupressure with nurse 26 27 provided counseling. Effect of acupressure was proved from day 2 to day 5, and the effect of 28 nurse advising on day 4 was approved and was close to the level of significance on day 29 5. Synergistic effects of P6 acupressure with nurse consultation is seen effective at reducing 30 CINV in patients with breast cancer. P6 acupressure along with counseling by nurses is a safe 31 and easy way to reduce nausea in patients. 32 33 7 The aim of the study Dibble (2007) was to compare differences in nausea and vomiting 34 (CINV) among the three groups of women with acupressure, placebo acupressure and 35 36 conventional care undergoing chemotherapy for breast cancer. This study was a randomized 37 clinical trial was conducted in a cancer center affiliated with the University of Texas. 160 women 38 with breast cancer undergoing chemotherapy with moderate nausea were studied. Inclusion 39 criteria of the study were women who received with or without fluorouracil 40 with with uorouracil paclitaxel or docetaxel, or 5FL, , and 41 cyclophosphamide for the treatment of breast cancer and nausea severity score with the last 42 43 chemotherapy at least 3 (average) at evaluation of the following day and tendency to participate 44 in the study. Subjects were randomly assigned to one of three groups. All patients were studied 45 for 21 days and the symptoms of nausea and vomiting were recorded. The used tool was Rhodes 46 Index of Nausea. In addition, nausea was scored using rating scale numerical description (NRS) 47 from 0 (no nausea) to 10 (worst imaginable nausea). Acupressure for nausea treatment involves 48 49 the use of digital pressure to one of the points located on both forearms using the thumb for 6 50 minutes in the morning and 3 minutes during the day. Pressure in the placebo group was entered 51 in the area except wrist. Acupressure was taught to nurses and the researcher by educational 52 films. Overall m of the massage was over 4 hours in a month. Initially, total number of samples 53 was 256 samples and 96 patients were excluded because of the severity of illness and lack of 54 desire to continue the study. 54 patients in the usual care group and 53 patients in the placebo 55 56 group and 53 patients in the acupressure group were included. The results showed that the 57 reduction of nausea and vomiting was higher in P6 acupressure group, nausea in the acupressure 58 59 60 Page 7 of 12 International Journal of Nursing

1 2 3 group was reduced than the placebo group t = 3.13, P =0.002 odds ratio [OR = 1.3) or the usual 4 5 care group t = 4.81, P <0.0001, OR = 1.4)). 6 Acupressure group compared with placebo and usualcare was estimated with a reduction in rank 7 8 of nausea as follows: Acupressure group versus usual care, T = 4.56, P <0.0001, IRR = 1.11; 9 Acupressure RIN versus placebo = 0.008, IRR = T = 2.68, P1.07; NRS nausea: Acupressure 10 versus usual care, T = 4.43, P < 0.0001, IRR = 1.11, nausea: NRS Acupressure versus placebo, T 11 = 2.14, P = 0.03, IRR = 1.06). Overall, there is no significant differences in demographics and 12 disease among the three groups, there was no statistically significant difference in acute nausea 13 14 or nausea and vomiting by treatment group as compared with other groups. Severity of nausea 15 and delayed vomiting rates (2 to 11 days after chemotherapy) was reduced in the acupressure 16 group than in the other two groups. Severity of nausea and vomiting in the placebo and usual 17 care groups had not significantly different. 18 For Peer Review 19 8 The aim of the study of Debille (2000) was to compare the severity of nausea and vomiting in 20 breast cancer patients undergoing chemotherapy. For this reasons, two groups of patients were 21 studied. First group of patients was those patients treated with acupressure and the second group 22 23 of patients was those who only received usual care. For this, 17 women within 21 to 28 days 24 were studied in a randomized clinical trial. Inclusion conditions was having CMF regimen or 25 doxorubicin, having nausea in previous treatments and fluency in English. Demographic 26 information and disease information questionnaire and assessment tools for nausea and vomiting 27 nausea Rhodes from the range 0 to 12 were used as the research tool and over the past 24 hours 28 was measured from 0 to 10. Another tool was chemotherapy problems checklists that was 29 30 completed patients by the patients. Before starting chemotherapy, all participants completed a 31 questionnaire about their demographics and disease. Treatment group was trained to acupressure, 32 and pressure points of patients’ wrist and knee was where under pressure for 3 minutes. There 33 was significant difference in the severity of nausea in the acupressure group than in the usual 34 care there. F = 10.4, p = 0.005, but was observed no significant differences in the questionnaire 35 36 of problems during chemotherapy in the two groups. F = 0.042, p = 0.08, Nausea average of the 37 acupressure group and the control group in the last month were 8.2 and 3, respectively. 38 39 Table1 Characteristics of the studies along with response rates and outcomes of massage 40 therapy 41 Th 42 The e 43 The Technique response Type sa 44 Researc study A s of Type of Type of chemotherapy rate and 45 of mp hers populati ge Massage Cancer regimens Massage 46 study le on Therapy Therapy 47 siz outcome 48 e 49 50 epirubucin 75 mg / m2 51 (Pharmalink Women AB, Uppland V Meaningfu 52 Billhult with soft Breast äsby, Sweden),fluorou l 53 RCT 69 39 (2007) breast strokes Cancer racil 600mg / (P = 54 33 55 cancer m2 (Mayne Pharma 0.025) 56 Plc, Warwickshire, 57 United 58 59 60 International Journal of Nursing Page 8 of 12

1 2 3 Kingdom),cyclophosp 4 5 hamide600 mg / 6 m2(Baxter 7 MedicalAB, Kista, 8 Sweden) every third 9 week for a total of 10 seven sessions. 11 Patients receiving 12 referred Types of reduction 13 Post Swedish chemotherapy with an to the chemoth of nausea 14 White RCT 83 230 massage identical repeating, chemot erapy without 15 (2003). 27 protocol cycle for 2 or more herapy cancers significant 16 remaining cycle 17 clinic 18 For Peer Review Acupressu 19 reBand: Patients 20 N Acupressu Meaningfu referred Types of 21 ot reBand l Roscoe to the chemoth cisplatin or 22 RCT lis 700 &Acustim (P = 0.05) (2003) chemot erapy doxorubicin 23 te ulation Acustimul 24 herapy cancers d Bands ation 25 clinic 26 Bands: 27 N / S 28 Cancers Patients M Reliefban 29 Grealis, of the significant with ea d: P6 30 Laurie RCT 42 reproduc Unknown reduction genital n acupunctu 31 (1999). tive of nausea cancer. 58 re point 32 system 33 34 Women effleurage 35 with strokes, to breast either 36 Meaningfu Pearl cancer 51 their foot / Breast 37 RCT 39 l 38 (2007). treated .8 lower leg Cancer P <0.05 39 with or to their 40 chemot hand / 41 herapy lower arm 42 43 Women 44 with O 45 breast ve Suh cancer r P6 Meaningfu 46 Breast EE(201 RCT in the 18 120 acupressu l 47 Cancer 48 2), first ye re P <0.05 49 cycle of ar 50 chemot s 51 herapy 52 Women O 53 acupressu Debille with ve Breast 54 RCT 160 re to P6 N / S (2007). breast r Cancer 55 point 56 cancer 18 57 Debille RCT. Outpati O 18 Acupressu Carcino Doxorubicin , Meaningfu 58 59 60 Page 9 of 12 International Journal of Nursing

1 2 3 2000). pilot ent ve rep6 & ma and Cyclophosphamide, l 4 5 cancer r ST36 Adnokar methotrexate, P <0.01 6 clinic 18 Synom fluorouracil 7 ye 8 ar 9 s 10 11 Discussion and conclusions 12 13 Nausea and vomiting are very common, yet debilitating side effects of cancer treatments. Results 14 of this study corroborates the notion that according to the studies differences in the type of 15 chemotherapy, type of interventions, measurement tools and the described results, a more studies 16 are needed and it is needed to done more research in each group with different cancer and also 17 with different chemotherapy treatments. 18 For Peer Review 19 In response to the first objective of this study: should be noted that only two of the 8 studies did 20 not show significant results regarding the effect of massage therapy on nausea and vomiting in 21 22 patients with cancer undergoing chemotherapy. Perhaps this lack of difference is related to the 23 use of different questionnaires and in some cases to the less sample size. If the authors had used 24 the specific tools, effect and the results obtained from interventions was found to be an effective 25 intervention. On the other hand, given that in 4 of 5 trials that had used pressure massage 26 technique and the results were significant, perhaps it can be say that massage of acupressure 27 possibly is effective on nausea and vomiting caused by chemotherapy, but as mentioned above, 28 29 due to differences in the studies, it cannot be considered conclusively. As well, all of the 8 30 studies reported loss of the subjects, and this issue show results in more realistic and due to the 31 fact that the interference in the case of cancer, various types of studies is limited and due to the 32 combination of chemotherapy, further studies are requires. 33 34 In response to the second goal of the study, however, due to the limited number of studies have 35 wrought on nausea and vomiting variables, cannot be conclusively stated this issue. However, 36 since 5 of the 8 studies were conducted on women with breast cancer and a study on 37 38 gynecological cancers and two studies on various types of cancers, perhaps it can be said that 39 massage therapy influence nausea and vomiting caused by chemotherapy in cancer of the breasts, 40 however, further studies are needed. So to confirm this reasoning, studies with larger sample size 41 than previous research is needed. The limitations of the conducted studies is that none of the 42 study on nausea and vomiting women patients at different stages of chemotherapy has not been 43 44 studied and there is not the possibility of comparing the effectiveness of interventions at different 45 stages of chemotherapy and further randomized controlled trials need to investigate this 46 difference. 47 48 Regarding to the third objective: Since chemotherapy regimens in the studies were not the same, 49 cannot be said that how massage therapy is effect on nausea and vomiting in the different 50 regimens of chemotherapy. 51 52 However, there are no systematic investigation without limitation and this case study is also not 53 excluded. Firstly because in some studies, although interventions have been mentioned as an 54 effective tool in reducing nausea and vomiting, but the most difference are defined close to the 55 56 level of the significant border (P = 0.05) . However, there is the possibility of more comparative 57 58 59 60 International Journal of Nursing Page 10 of 12

1 2 3 studies on the interventions methods in the present studies that may be are not considered 4 5 here. However, although all expressed positive results but further studies are needed. 6 The present systematic review Despite confirmation of the effect of massage therapy methods on 7 8 nausea and vomiting in 6 cases of the 8 papers could not have review and approve the positive 9 effects of these methods on all types of cancers, all types of chemotherapy regimens and in all 10 studies conducted in different countries and however, due to different conditions are not 11 retractable and metaanalysis in all studies. Since this study was only conducted research and 12 published in English and engage in many valid sites, it seems according to appropriate method of 13 14 conducted trials, the noted interventions can be useful to improve the nausea and vomiting of 15 breast cancer to a large extent, and since the fact that the implementation of these complementary 16 methods are inexpensive and easy to learn and perform and harm to patients, it can be considered 17 for complementary and nursing treatment in the cancer treatment centers. 18 For Peer Review 19 20 21 22 23 Reference 24 1. Yoo HJ, Ann SH, Kim SB. Efficacy Of Muscle Relaxation Training And Guided Imagery 25 In Reduce Chemotherapy Side Effect In Patient With Breast Cancer And In Improving 26 Their Quality Of Life. support care cancer 2005; 13(10): 82633. 27 28 2. Joan Klein, Peter Griffiths Acupressure for nausea and vomiting in cancer patients 29 receiving chemotherapy Brtlish Journal o1 Community Nursing. 2004. Vol 9, No 9 30 Safety and Efficacy of Massage Therapy for Patients With Cancer ,Cancer وLisa Corbin .3 31 32 33 Control. July 2005, Vol. 12, No. 3 34 35 4. Carner j, Baily C. Cancer Nursing Care in Context, Black well 2001; 2016, 350 7. 11. 36 Lackmann Medical Surgical nursing 3. translation by; Ebrahimi N. chapter 4, 1 Ed, 37 Tehran, 1383: 285334. 38 39 5. Grundy M. Nursing In Hematology Oncology, chapter 15, 2th ED, Bailler Tindal 2001; 40 2118. 41 42 6. Ahles TA, Tope DM, Pinkson B. Massage Therapy For Patient Undergoing Autologous 43 Bone Marrow Transplantation. J pain symptom manage 1999; 18(3): 157 6347. 44 45 7. Janice PostWhite and et all,2003 Therapeutic Massage and Healing Touch Improve 46 47 Symptoms in Cancer INTEGRATIVE CANCER THERAPIES 2(4); 2003 pp. 332344 48 49 8. Deborah Hughes and et all 2008 Massage Therapy as a Supportive Care Intervention for 50 Children With Cancer Oncology Nursing Forum – vol 35, no 3, 2008 51 52 9. Lewis, S.M., Heitkemper, M.M., Dirksen, S.R. (2000). Medical Surgical Nursing. 5th 53 ed. Mosby Co, PP: 269271. 54 55 10. Fellowes D, Barnes K, Wilkinson S 2008 Aromatherapy and massage for symptom relief 56 in patients with cancer (Review) 1 Copyright © 2008 The Cochrane Collaboration. 57 Published by JohnWiley & Sons, Ltd 58 59 60 Page 11 of 12 International Journal of Nursing

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1 2 3 Vomiting Near the End of Life: A Systematic Review.J Pain Symptom Manage;20:374– 4 5 387. 6 7 26. http://www.ncii.ir/Articles.aspx?p=77 8 9 10 11 12 13 14 15 16 17 18 For Peer Review 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60